Peptides containing one or more backbone modifications often have improved stability toward proteolytic degradation, and diverse conformational, electronic, and solubility properties. We propose to continue our systematic evaluation of the conformational properties of model cyclic pseudopeptides, evaluate new synthetic procedures for their preparation, and investigate the biological consequences of amide bond replacements in several small cyclic bioactive parents, including cyclo (Pro-Phe-Met-Gly-D-Trp-Met), a recently described CCK analog with selective central receptor affinity, in small, potent, somatostatin analogs, and later in other appropriate hosts. Modified cyclic pseudopeptides represent potentially useful species for new peptide-based drug candidates as well as for selective enzyme inhibitors. But these compounds also provide an alternative approach for novel macrocycle preparation with stereochemically defined side chain constituents. The macrocycles to be prepared will incorporate psi(CH2S), psi(CH2NH), and psi(CSNH) amide surrogates, and side chain functionalities will include both acidic and basic constituents. Following complete structural and conformational characterization, the possibility of selective ion coordination or customized catalytic activity will also be investigated. The hypothesis that effective enzyme mimetics may be best fashioned from a combination of amino acid and modified amino acid structures will be a central theme of our experimental approach.